Therapeutic effects of TP5, a Cdk5/p25 inhibitor, in in vitro and in vivo models of Parkinson’s disease

Tran, Judith; Taylor, Shane K. B.; Gupta, Abhinav; Amin, Niranjana D.; Pant, Harish C.; Gupta, Bhagwati P.; Mishra, Ram K.

doi:10.1016/j.crneur.2021.100006

Cited by 5 publications

(3 citation statements)

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“… 48 Moreover, a derivative of p35 activator truncated peptide 5 (TP5) has a neuroprotective effect in PD model by inhibiting Cdk5/p25. 49 AAV9‐CIP improves both motor and non‐motor disorders in PD. 47 It has been demonstrated that melatonin attenuates MPTP neurotoxicity and inhibition of apoptosis through suppression of calpain/Cdk5 signalling pathway.…”

Section: Role Of Calpain/cdk5 Inhibitors In Pdmentioning

confidence: 97%

“…Cdk5 inhibitor AAV9‐CIP prevents degeneration of dopaminergic neurons of the SNpc in MPTP‐induced PD mouse model 48 . Moreover, a derivative of p35 activator truncated peptide 5 (TP5) has a neuroprotective effect in PD model by inhibiting Cdk5/p25 49 . AAV9‐CIP improves both motor and non‐motor disorders in PD 47 .…”

Section: Role Of Calpain/cdk5 Inhibitors In Pdmentioning

confidence: 99%

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Cyclin‐dependent kinase 5 (CDK5) inhibitors in Parkinson disease

Alrouji,

Al‐kuraishy,

Al‐Gareeb

et al. 2024

J Cellular Molecular Medi

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Cyclin‐dependent kinase 5 (Cdk5) is a protein expressed in postmitotic neurons in the central nervous system (CNS). Cdk5 is activated by p35 and p39 which are neuron regulatory subunits. Cdk5/p35 complex is activated by calpain protease to form Cdk5/p35 which has a neuroprotective effect by regulating the synaptic plasticity and memory functions. However, exaggerated Cdk5 is implicated in different types of neurodegenerative diseases including Parkinson disease (PD). Therefore, modulation of Cdk5 signalling may mitigate PD neuropathology. Therefore, the aim of the present review was to discuss the critical role of Cdk5 in the pathogenesis of PD, and how Cdk5 inhibitors are effectual in the management of PD. In conclusion, overactivated Cdk5 is involved the development of neurodegeneration, and Cdk5/calpain inhibitors such as statins, metformin, fenofibrates and rosiglitazone can attenuate the progression of PD neuropathology.

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Section: Role Of Calpain/cdk5 Inhibitors In Pdmentioning

confidence: 97%

Section: Role Of Calpain/cdk5 Inhibitors In Pdmentioning

confidence: 99%

Cyclin‐dependent kinase 5 (CDK5) inhibitors in Parkinson disease

Alrouji,

Al‐kuraishy,

Al‐Gareeb

et al. 2024

J Cellular Molecular Medi

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“…Viral-mediated expression of dominant-negative Cdk5 or a peptide inhibitor of Cdk5 prevents the death of dopaminergic neurons in the MPTP mouse model [ 131 , 132 ]. Similarly, a Cdk5 peptide inhibitor blocks Cdk5 hyperactivity and promotes dopaminergic neuronal survival in the nematode worm C. elegans after exposure to paraquat [ 133 ].…”

Section: Dysregulation Of Cdk5: Calpain-dependent Proteolytic Cleavage Of P35 To P25mentioning

confidence: 99%

Three decades of Cdk5

Pao

Tsai

2021

J Biomed Sci

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Cdk5 is a proline-directed serine/threonine protein kinase that governs a variety of cellular processes in neurons, the dysregulation of which compromises normal brain function. The mechanisms underlying the modulation of Cdk5, its modes of action, and its effects on the nervous system have been a great focus in the field for nearly three decades. In this review, we provide an overview of the discovery and regulation of Cdk5, highlighting recent findings revealing its role in neuronal/synaptic functions, circadian clocks, DNA damage, cell cycle reentry, mitochondrial dysfunction, as well as its non-neuronal functions under physiological and pathological conditions. Moreover, we discuss evidence underscoring aberrant Cdk5 activity as a common theme observed in many neurodegenerative diseases.

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